Sequential expression of miR-221-3p and miR-338-3p in Schwann cells as a therapeutic strategy to promote nerve regeneration and functional recovery  

作　　者：Li-Li Wen Tian-Hao Yu Yi-Zhan Ma Xiao-Yan Mao Tian-Rang Ao Rabia Javed Hirotomo Ten Akira Matsuno Qiang Ao 

机构地区：[1]Department of Tissue Engineering,School of Intelligent Medicine,China Medical University,Shenyang,Liaoning Province,China [2]The VIP Department,School and Hospital of Stomatology,Liaoning Provincial Key Laboratory of Oral Diseases,China Medical University,Shenyang,Liaoning Province,China [3]Department of Oncology,Cancer Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing,China [4]Department of Neurosurgery,Teikyo University School of Medicine,Tokyo,Japan [5]NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterial&Institute of Regulatory Science for Medical Device&National Engineering Research Center for Biomaterials,Sichuan University,Chengdu,Sichuan Province,China

出　　处：《Neural Regeneration Research》2023年第3期671-682,共12页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.81771351;the National Key R&D Program of China,No.2017YFA0105802;the Joint Research Fund Liaoning-Shenyang National Laboratory for Materials Science,No.2019JH3/30100022;the National Science Foundation for Post-doctoral Scientists of China,No.2018M641732(all to QA and LLW)。

摘　　要：The functional properties of endogenous Schwann cells(SCs)during nerve repair are dynamic.Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the repair of damaged nerves.Previous studies showed that miR-221-3p promotes the proliferation and migration of SCs,and miR-338-3p promotes the myelination of SCs.In this study,we established rat models of sciatic nerve injury by bridging the transected sciatic nerve with a silicone tube.We injected a miR-221 lentiviral vector system together with a doxycycline-inducible Tet-On miR-338 lentiviral vector system into the cavity of nerve conduits of nerve stumps to sequentially regulate the biological function of endogenous SCs at different stages of nerve regeneration.We found that the biological function of SCs was sequentially regulated,the diameter and density of myelinated axons were increased,the expression levels of NF200 and myelin basic protein were increased,and the function of injured peripheral nerve was improved using this system.miRNA Target Prediction Database prediction,Nanopore whole transcriptome sequencing,quantitative PCR,and dual luciferase reporter gene assay results predicted and verified Cdkn1b and Nrp1 as target genes of miR-221-3p and miR-338-3p,respectively,and their regulatory effects on SCs were confirmed in vitro.In conclusion,here we established a new method to enhance nerve regeneration through sequential regulation of biological functions of endogenous SCs,which establishes a new concept and model for the treatment of peripheral nerve injury.The findings from this study will provide direct guiding significance for clinical treatment of sciatic nerve injury.

关 键 词：cdkn1b MIR-221 miR-338 miRNA nerve regeneration NRP1 peripheral nerve injury REGULATION Schwann cells sequential expression 

分 类 号：R741[医药卫生—神经病学与精神病学]